PRINCIPLES THAT MAKE ORGAN TRANSPLANTS WORK

Organ transplantation and renal failure management are critical components of modern medicine involving multidisciplinary approaches, precise diagnostic criteria, and timely interventions.

1. Principles of Transplantation and Organ Donation

1.1 Definition and Overview

• Organ Transplantation: The surgical procedure of transferring an organ from a donor to a recipient to restore function in patients with end-stage organ failure.
• Organ Donation: The process by which a donor’s organs are retrieved post-mortem or from living donors to benefit recipients.

1.2 Fundamental Principles

• Immunological Compatibility: Matching donor and recipient tissue types (especially Human Leukocyte Antigen, HLA) to reduce rejection risks.
• Timing: Optimizing organ retrieval and transplantation within viable ischemic periods to enhance graft survival.
• Consent and Ethical Considerations: Ensuring informed consent in living donations and adherence to ethical frameworks and legal regulations in cadaveric donations.
• Preservation and Transport: Utilizing cold preservation techniques and rapid transport to maintain organ viability.

1.3 Organ Donation Pathways

• Deceased Donor Donation: Harvesting organs after confirmation of brain stem death or circulatory death.
• Living Donor Donation: Elective removal of organs or tissue such as kidney or liver segments from healthy donors, with thorough assessment for donor safety.

2. Criteria for Diagnosis of Brain Stem Death and Circulatory Death

2.1 Brain Stem Death (BSD)

• Definition: Irreversible cessation of all brain stem functions, implying the individual has no potential for recovery.
• Diagnostic Criteria:
  • Clinical Examination:
    • Coma with known cause capable of causing brain death.
    • Absence of cerebral and brainstem reflexes including pupillary light response, corneal reflex, vestibulo-ocular reflex, gag and cough reflexes.
    • Apnea test demonstrating the absence of spontaneous respiration while maintaining adequate arterial CO₂ to stimulate breathing.
  • Exclusion Criteria:
    • Hypothermia (temperature ≥ 36°C).
    • Normal blood pressure and absence of CNS depressant drugs.
    • Metabolic and endocrine disturbances corrected.
  • Confirmatory Tests (when clinical tests are inconclusive or confounded):
    • Electroencephalogram (EEG showing electrocerebral silence).
    • Cerebral blood flow studies (e.g., radionuclide angiography).
• Brain Stem Death as Legal Death: Brain stem death is recognized as legal death in many jurisdictions, allowing organ retrieval.

2.2 Circulatory Death

• Definition: Permanent cessation of circulatory and respiratory functions.
• Criteria:
  • Irreversible cardiac arrest leading to lack of circulation to the brain and other organs.
  • Absence of pulse and spontaneous breathing confirmed after an appropriate observation period (usually 2-5 minutes).
  • Use of advanced cardiac monitoring devices for confirmation.
• Significance: Increasingly relevant for organ donation protocols (DCD: Donation after Circulatory Death).

3. Diagnosis, Assessment, and Initial Management of Renal Failure / Acute Kidney Injury (AKI)

3.1 Definition and Classification

• Acute Kidney Injury (AKI): Sudden decline in kidney function leading to impaired waste excretion, fluid, and electrolyte imbalance.
• Classification (KDIGO Criteria):
  • Stage 1: Serum creatinine increase ≥ 0.3 mg/dL or 1.5–1.9 times baseline.
  • Stage 2: 2.0–2.9 times baseline.
  • Stage 3: ≥ 3 times baseline or initiation of renal replacement therapy.

3.2 Diagnostic Approach

• Clinical History and Examination:
  • Assess for pre-renal causes (hypovolemia, hypotension), intrinsic renal disease (glomerulonephritis, nephrotoxins), post-renal obstruction.
  • Identify symptoms such as oliguria, edema, and other systemic signs.
• Laboratory Tests:
  • Serum creatinine and urea levels.
  • Electrolytes (focus on potassium).
  • Urinalysis (proteinuria, hematuria).
  • Fractional excretion of sodium (FENa) to differentiate pre-renal vs intrinsic causes.
• Imaging:
  • Renal ultrasound to exclude obstruction and assess kidney size.

3.3 Initial Management

• Stabilization:
  • Ensure airway, breathing, and circulation (ABCs).
  • Correct hypovolemia with intravenous fluids if indicated.
  • Manage electrolyte imbalances, e.g., hyperkalemia urgently with calcium gluconate, insulin with glucose, bicarbonate.
  • Adjust or stop nephrotoxic medications (NSAIDs, ACE inhibitors).
• Monitoring:
  • Hourly urine output and daily weight.
  • Continuous vital sign monitoring and fluid balance charts.
• Multidisciplinary Coordination:
  • Referral to nephrology for assessment and planning renal replacement therapy if indicated.
  • Collaboration with critical care specialists in ICU settings.
  • Involve urology if obstruction suspected.

4. Indications for and Principles of Haemodialysis and Peritoneal Dialysis

4.1 Indications for Dialysis in AKI and Chronic Kidney Disease (CKD)

• Absolute Indications:
  • Refractory hyperkalemia.
  • Severe metabolic acidosis unresponsive to medical therapy.
  • Uremic complications such as pericarditis, encephalopathy.
  • Fluid overload causing pulmonary edema resistant to diuretics.
  • Certain drug overdoses.

4.2 Principles of Haemodialysis

• Mechanism: Blood is circulated extracorporeally through a dialyzer where solute and fluid exchange occurs across a semipermeable membrane via diffusion and ultrafiltration.
• Vascular Access:
  • Arteriovenous fistulas preferred for long-term use.
  • Central venous catheters for temporary access.
• Treatment Parameters:
  • Frequency and duration depend on patient condition.
  • Anticoagulation typically used to prevent clotting in the extracorporeal circuit.
• Advantages:
  • Rapid removal of toxins and fluid.
  • Controlled correction of electrolyte disturbances.
• Limitations:
  • Requires vascular access and specialized machines.
  • Risk of hemodynamic instability during sessions.

4.3 Principles of Peritoneal Dialysis (PD)

• Mechanism: Utilizes the patient’s peritoneal membrane as a semipermeable membrane where dialysate is infused into the peritoneal cavity. Solutes and excess fluid move from blood vessels into the dialysate by diffusion and osmosis.
• Types:
  • Continuous Ambulatory Peritoneal Dialysis (CAPD) – manual exchanges done throughout the day.
  • Automated Peritoneal Dialysis (APD) – machine-assisted exchanges typically overnight.
• Access: Placement of a permanent Tenckhoff catheter in the abdominal cavity.
• Advantages:
  • Greater patient mobility and independence.
  • Gentle fluid and solute removal.
  • Suitable where vascular access is problematic.
• Limitations:
  • Risk of peritonitis.
  • Less efficient for rapid toxin removal.
  • May be contraindicated in patients with abdominal adhesions or hernias.

Conclusion

The principles of transplantation and organ donation are grounded not only in surgical expertise but in the ethical and clinical frameworks that govern brain stem and circulatory death diagnosis. Acute kidney injury requires prompt, systematic assessment and multidisciplinary coordination to prevent progression and manage complications. Dialysis, encompassing haemodialysis and peritoneal dialysis, plays a pivotal role in managing renal failure, with modality selection tailored to patient needs and clinical context. Understanding these core medical principles is essential for delivering optimal patient care and improving outcomes in complex cases involving organ failure and transplantation.